Many laboratory and clinical procedures involve processing a sample to separate a target from the sample for subsequent identification and analysis of the target. Such processes are commonly used to detect of wide range of targets, including biological entities such as cells, viruses, proteins, bacterium, nucleic acids, etc. and have applications in clinical diagnostics, biohazard screenings, and forensic analyses.
Often there is an immediate need to identify the target, whether to determine the proper course of treatment or to develop response protocol for biohazard threat. For example, blood-borne pathogens are a significant healthcare problem because a delayed or improper diagnosis can lead to sepsis. Sepsis, a severe inflammatory response to infection, is a leading cause of death in the United States. Early detection of the blood-borne pathogens underlying the infection is crucial to preventing the onset of sepsis. With early detection, the pathogen's drug/antibiotic resistant profile can be obtained which allows the clinician to determine the appropriate anti-microbial therapy for a quicker and more effective treatment.
One method of isolating a pathogen or target from a sample is performing a detection assay on a processing cartridge or lab-on-chip, which are typically microfluidic. A problem with identifying targets in sample using the cartridge is the inability to transfer the entire sample from the sample container. Typically, sample is introduced into a cartridge via pipetting or tubing, which often leaves sample in the sample container and/or loses sample during the transfer process. The failure to transfer the entire sample can lead to loss of critically relevant sample (i.e. sample with sufficient levels of targets for capture) and can result in a failure to isolate a target/pathogen simply because a portion of sample that contained the target was left in the sample container or lost during sample transfer. This need to transfer the entire sample is of critical importance when there is little sample, as often the case for forensic analysis, or when there is a small concentration of targets per mL (e.g. 1 CFU/mL), as in the case of pathogens during active blood-borne infection or after antibiotic treatment.
One solution to processing samples with low concentrations of targets per mL is to enrich the sample prior to introducing the sample for processing to increase the pathogen or target levels. By increasing concentration of targets per mL of sample, the likelihood that a small portion of the sample contains the target increases. This reduces risk of a failing to process clinically relevant sample simply because the sample was not entirely transferred. However, these enrichment steps require a significant amount of time and can potentially compromise test sensitivity by killing some of the cells sought to be measured. In certain cases, a full week may be necessary to reach the desired levels of target, such as a sepsis causing pathogen. Unfortunately, the time needed for enrichment is often not an option for a septic patient.
Because the failure to rapidly isolate a target may be linked to a failure to transfer clinically relevant sample into a processing device, there is a need to develop a method and device for maximizing the amount of sample transferred from a sample container into a cartridge for subsequent processing.